Impairment in auditory functions has been repeatedly reported in comatose patients (Fischer et al., 1999) and minimally conscious or vegetative state patients (Boly et al., 2011). Typically, these clinical populations show deficits in neural discrimination between repeated (standard) and rare (deviant) sounds as measured by electroencephalography (EEG) (Näätänen et al., 1978). The degree of discrimination between standard and deviant sounds is quantified by first computing the average of the EEG responses (Auditory Evoked Potentials, AEPs) to standard and deviant sounds. The difference of the average AEPs to the two types of sounds manifests typically at fronto-central electrodes and at ˜100-150 ms after the onset of deviation (Fischer et al., 1999; Todd et al., 2007; Wijnen et al., 2007; Garrido et al., 2009) and it is usually referred to as mismatch negativity (MMN) EEG component.
In previous studies on MMN in comatose patients, MMN evaluation requires the identification of a robust average Auditory Evoked Potential (AEP) in response to sounds (i.e. a significant modulation with respect to baseline of the average AEP at about 100 ms post-stimulus onset). Therefore, data from a large percentage of patients are systematically disregarded (e.g. ˜33% in one study by Fischer et al., 1999). Furthermore, this assessment requires an a priori hypothesis of the latency and the magnitude of AEP responses. In pathological conditions, making such hypotheses can be challenging, as AEPs can exhibit high inter-individual variability and differ from those of healthy subjects.
Interestingly, MMN appears to be absent in those comatose patients who do not awake from the coma. Therefore, the presence of the MMN is considered to be a predictor of awakening, with high predictive value for awakening (Fischer et al., 2004). However, because this experimental evidence is assessed at various delays after coma onset, it is still unclear whether this deficit is independent of the time of the recording. Moreover, post-anoxic comatose patients are nowadays often treated with mild induced Therapeutic Hypothermia (TH) which is known to have neuro-protective effects on the patients and to increase their chance of survival, but its effect on brain functions remains unknown.
At present, all the tests implemented in the clinical practice are informative of the chance of dying. Specifically, lack of return of brainstem reflexes at 72 hours, early myoclonus, and bilateral absence of early cortical somatosensory evoked potentials (SSEPc) have robust predictive value for death (Bouwes et al., 2009; Fugate et al., 2010; Rossetti et al., 2010).
Therefore, an object of the present invention is to propose a method performed during the very early phase of coma for predicting awakening in a comatose patient treated with TH protocol.
Another object of the present invention is to propose a robust method for predicting awakening in a comatose patient.
Another object of the present invention is to propose a computer-implemented method thereof.